E-GEOD-6135 - LKB1 modulates lung cancer differentiation and metastasis
Released on 28 August 2007, last updated on 2 May 2014
Homo sapiens, Mus musculus
Inherited mutation in LKB1 results in the Peutz-Jeghers syndrome (PJS), characterized by intestinal hamartomas and a modestly increased frequency of gastrointestinal and breast cancer1. Somatic inactivation of LKB1 occurs in human lung adenocarcinoma2-4, but its tumor suppressor role in this tissue is unknown. Here we show that somatic Lkb1 deficiency strongly cooperates with somatic K-rasG12D activating mutation to accelerate the development of mouse lung tumorigenesis. Lkb1 deficiency in the setting of K-rasG12D mutation (K-ras Lkb1L/L) was associated with decreased tumor latency and increased tumor aggressiveness including metastasis. Furthermore, tumors from K-ras Lkb1L/L mice demonstrated histologies--squamous, adenosquamous and large cell--not seen with K-rasG12D mutation, Ink4a/Arf inactivation, or p53 inactivation alone or in combination. Experiments in vitro suggest that LKB1 suppresses lung tumorigenesis and progression through both p16INK4a-ARF-p53 dependent and independent mechanisms. These data indicate that LKB1 regulates lung tumor progression and differentiation. Keywords: cancer research To analyze the role of LKB1 in lung cancer progression and differentiation, we have dissected the lung tumors from mice with/without lkb1 loss and performed the microarray analyses to compare their gene expression pattern. In addition, we have also performed microarray analysis in both A549 and H2126 cell lines after reconsistitution of either wt-lkb1 or the kinase dead form of lkb1 (lkb1-KD) to confirm what we observed from in vivo studies.
transcription profiling by array
kwok-kin wong <email@example.com>, Bruce Johnson, Chad Torrice, Cheng Fan, Cristina Contreras, Danan Li, David C Christiani, David J Kwiatkowski, Diego H Castrillon, Dongpo Cai, Geoffrey I Shapiro, George N Naumov, Hongbin Ji, Janakiraman Krishnamurthy, Jussi Koivunen, Kate McNamara, Kwok-Kin Wong, Lei Bao, Liang Chen, Lucian R Chirieac, Matthew Meyerson, Matthew R Ramsey, Mei-Chih Liang, Michael C Wu, Nabeel Bardeesy, Neal I Lindeman, Neil D Hayes, Norman E Sharpless, Pasi A Ja¨nne, Piotr Kozlowski, Robert Padera, Roderick T Bronson, Samanthi Perera, Takeshi Shimamura, Xihong Lin
LKB1 modulates lung cancer differentiation and metastasis. Ji H, Ramsey MR, Hayes DN, Fan C, McNamara K, Kozlowski P, Torrice C, Wu MC, Shimamura T, Perera SA, Liang MC, Cai D, Naumov GN, Bao L, Contreras CM, Li D, Chen L, Krishnamurthy J, Koivunen J, Chirieac LR, Padera RF, Bronson RT, Lindeman NI, Christiani DC, Lin X, Shapiro GI, Jänne PA, Johnson BE, Meyerson M, Kwiatkowski DJ, Castrillon DH, Bardeesy N, Sharpless NE, Wong KK. , Europe PMC 17676035